The project was approved in the Fall of 2013. Over the last year we completed data acquisition on the full sample (80 subjects; mixed population of patients and controls). The established protocol investigated brain mechanisms of placebo response in chronic pain. A group of patients with chronic widespread pain (fibromyalgia) were compared to matched healthy controls. Subjects were recruited through IRB-approved NIH Clinical Trial recruiting line, social media postings, and via advertisements placed around the main NIH campus and in local newspapers. In this randomized double-blinded study, each subject participated in two sessions separated by 1-7 days. The first session included familiarization and training using psychophysical methods in a mock scanner environment. The second session included testing in the MRI environment. During the second session, the effect of intravenous administration of naloxone on the placebo effect was tested. Subjects were randomly assigned to either a saline or naloxone condition. We have begun analysis of the acquired data to test the following hypotheses: 1) Healthy individuals will show stronger placebo analgesia than chronic pain patients; 2) there will be a positive correlation between the amount of gray matter reduction in placebo-relevant brain regions and reduction in placebo responsiveness in chronic pain patients relative to healthy subjects; 3) compared to healthy subjects, chronic pain patients will have lower levels of brain activity in placebo-relevant brain regions during periods of anticipation of pain relief and the degree of decreased anticipatory activity will correlate with the decrease in magnitude of placebo analgesia; and 4) blocking endogenous opioid activity, by administering the opioid receptor antagonist naloxone, will reduce placebo analgesia in healthy subjects, but not at all or to a lesser extent in chronic pain patients. Correspondingly, brain activity in placebo-relevant brain regions will be reduced by naloxone in healthy subjects but not in pain patients.